Transcript Druggable Genome and Proteome

DRUGGABLE GENOME
AND PROTEOME
“the most fruitful basis for the discovery of a
new drug is to start
with an old drug” (James W Black, Nobel de
Medicina 1988)
Karen A. Méndez L
Druggability
Thomas H Keller, et al. Current Opinion in Chemical Biology 2006, 10:357–361
Drug- like compounds
Lipinski (2001) --˃ Rule of 5 (RO5)
Thomas H Keller, et al. Current Opinion in Chemical Biology 2006, 10:357–361
Rule of 5
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1. RO5 applies only to compounds that are
delivered by the oral route.
2. RO5 applies only to compounds that are
absorbed by passive mechanisms
3. There are important exceptions (MW and natural
compounds).
4. RO5 compliant compounds are not automatically
good drugs
Disease and Druggable Genome
Hopkins y Groom (2002)
Dixon SJ and Stockwell BR (2009)
Overington et al. Nature Reviews Drug Discovery 5, 993–996 (December 2006) | doi:10.1038/nrd2199
Druggable Proteome
Pharmaceutically Tractable Genome
Door: Protein
Lock: Drug Binding Site
Key: Drug
Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY
VOLUME 25 NUMBER 10 OCTOBER 2007
Druggable Network
Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY VOLUME 25 NUMBER 10 OCTOBER 2007
Distribution of Drugs and Drug Targets
Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY VOLUME 25 NUMBER 10 OCTOBER 2007
Distribution of Drugs and Drug Targets
Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY VOLUME 25 NUMBER 10 OCTOBER 2007
References
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Dixon SJ and Stockwell BR (2009) Identifying druggable disease-modifying
gene products, Curr Opin Chem Biol 13: 549–555
Yıldırım et al, Drug–target network. NATURE BIOTECHNOLOGY VOLUME
25 NUMBER 10 OCTOBER 2007
Overington et al. Nature Reviews Drug Discovery 5, 993–996 (December
2006) | doi:10.1038/nrd2199
Thomas H Keller, et al. Current Opinion in Chemical Biology 2006, 10:357–
361
Zheng CJ et al. (2006) Therapeutic Targets: Progress of Their Exploration
and Investigation of Their Characteristics,
Pharmacol Rev 58: 259–279
Russ AP and Lampel S (2005) The druggable genome:an update, Drug
Discov Today 10 (23/24): 1607-1610
Hopkins AL and Groom CR (2002) The druggable genome, Nat Rev Drug
Discov 1: 727-730